EP0146065B1 - Betamethazondipropionat-Creme - Google Patents

Betamethazondipropionat-Creme Download PDF

Info

Publication number
EP0146065B1
EP0146065B1 EP84114635A EP84114635A EP0146065B1 EP 0146065 B1 EP0146065 B1 EP 0146065B1 EP 84114635 A EP84114635 A EP 84114635A EP 84114635 A EP84114635 A EP 84114635A EP 0146065 B1 EP0146065 B1 EP 0146065B1
Authority
EP
European Patent Office
Prior art keywords
percent
composition
water
betamethasone dipropionate
white
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP84114635A
Other languages
English (en)
French (fr)
Other versions
EP0146065A3 (en
EP0146065A2 (de
Inventor
Richard K. Florance
Joel A. Sequeira
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme LLC
Original Assignee
Schering Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Corp filed Critical Schering Corp
Priority to AT84114635T priority Critical patent/ATE44462T1/de
Publication of EP0146065A2 publication Critical patent/EP0146065A2/de
Publication of EP0146065A3 publication Critical patent/EP0146065A3/en
Application granted granted Critical
Publication of EP0146065B1 publication Critical patent/EP0146065B1/de
Expired legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone

Definitions

  • This invention relates to a cream formulation of betamethasone dipropionate having improved properties.
  • U.S. Patent No. 4,070,462 discloses a steroid ointment having very good efficacy. The effectiveness of this composition is believed to be due to the complete dissolution of the steroid in the ointment. However, this ointment, like others, feels somewhat greasy when applied to the skin.
  • Another product currently on the market (Diprosone Cream) is an oil-in-water emulsion containing, in addition to betamethasone dipropionate, water, mineral oil, white petrolatum, ceteth 20, cetostearyl alcohol, monobasic sodium phosphate, and phosphoric acid, preserved with 4-chloro-m-cresol and propylene glycol. Although this formula is cosmetically more elegant than the previously discussed ointment, it is not as effective.
  • European Patent Application No. 84105109.7 filed May 5, 1984 discloses a cream-like composition having better efficacy than Diprosone Cream.
  • the present invention provides a betamethasone dipropionate cream formulation having cosmetic elegance and, very surprisingly, efficacy similar to the ointment of U.S. Patent No. 4,070,462. This is particularly unexpected in view of the fact that the present invention is in the form of a water-in-oil emulsion, throughout which the steroid is dispersed, i.e., the steroid is not completely dissolved. Furthermore, the composition are surprisingly stable for water-in-oil emulsions.
  • Some steroidal ointments have a tendency to suppress the hypopituitary adrenal (HPA) axis, causing a potentially dangerous decrease in the level of cortisol in the blood.
  • the present compositions show little, if any, tendency to cause HPA-axis suppression.
  • the present invention comprises an esthetically elegant topical composition for the treatment of inflammation in the form of a water-in-oil emulsion comprising by weight based on the total weight of the composition:
  • the formulations contain from 3 to 15 percent cyclomethicone (more preferably 5 to 10 percent).
  • the preferred buffer system comprises 0.3 percent monobasic sodium phosphate monohydrate and 0.001 percent phosphoric acid.
  • Other buffer systems for example a combination of citric acid monohydrate and trisodium citrate dihydrate or succinic acid and sodium hydroxide, may be used.
  • the preferred hydrophilic emulsifier is ceteth 20, in the amount of 0.01 to 2 percent, preferably 0.3 to 0.7 percent.
  • Other hydrophilic emulsifiers for use in the compositions include polyoxyethylene sorbitan mono-oleate, polyoxyethylene monostearate, polyoxyethylene lauryl ether, and polysorbate 60 and combinations thereof.
  • the preferred lipophilic emulsifier is glyceryl oleate in the amount of 1 to 5 percent, preferably 2 to 4 percent.
  • Other acceptable lipophilic emulsifiers include sorbitan tristearate, glyceryl stearate, propylene glycol stearate, sorbitan sesquioleate and combinations thereof.
  • the HLB is defined by Griffin, W. C., J. Soc. Cosmetic Chemist, 1, 311 [1949] and 5,249 [1954].
  • the HLB reflects the balance between hydrophilic and lipophilic strength of the emulsifiers. The higher HLB indicates a stronger hydrophilic tendency of the emulsification system.
  • the preferred preservative is 0.03 to 0.2 percent 4-chloro-m-cresol (preferably 0.07 to 0.12 percent).
  • Other acceptable preservatives include benzyl alcohol, sorbic acid, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, and combinations thereof.
  • the petrolatum can be white or yellow petrolatum and the beeswax can be white or yellow wax. However, for the sake of providing a white cream, these are preferably used as white petrolatum and white wax.
  • the sorbitol is conveniently mixed in as an aqueous solution, e.g. as a 70% solution of sorbitol in water.
  • Example 3 The ingredients are combined in a manner similar to that of Example 1.
  • Example 3 The ingredients are combined in a manner similar to that of Example 1.
  • Example 1 The ingredients are combined in a manner similar to that of Example 1.
  • Example 1 The ingredients are combined in a manner similar to that of Example 1.
  • formulations of the examples When applied to the skin, the formulations of the examples are found to be equivalent to the ointment of U.S. Patent No. 4,070,462, in vascoconstrictor and anti-inflammatory activity, despite their being in the form of an elegant cream rather than an ointment. Furthermore, formulations of the present invention have little or no tendency to suppress the HPA axis.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Saccharide Compounds (AREA)
  • Cosmetics (AREA)
  • Grain Derivatives (AREA)
  • Fats And Perfumes (AREA)
  • Confectionery (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (8)

1. Elegante topische Wasser-in-ÖI-Zusammensetzung zur Behandlung von Entzündungen, umfassend, als Gewicht bezogen auf das Gesamt-Gewicht der Zusammensetzung,
(a) 0,02 bis 0,1% Betamethason-dipropionat,
(b) 15 bis 40% Petrolatum,
(c) 3 bis 15% Bienenwachs,
(d) 3,5 bis 17,5% Sorbit, gelöst in dem vorhandenen Wasser,
(e) 2,5 bis 15% Propylenglycol,
(f) Puffer, um den pH der Zusammensetzung innerhalb des Bereichs von 3 bis 6 aufrechtzuerhalten,
(g) ausreichende Mengen wenigstens eines hydrophilen Emulgators und wenigstens eines lipophilen Emulgators, um die Emulsion zu stabilisieren und das Betamethason-dipropionat zu dispergieren, wobei der HLB-Wert der Emulgatoren innerhalb des Bereichs von 2 bis 8 liegt,
(h) eine ausreichende Menge eines dermatologisch annehmbaren Konservierungsmittels, um einen Abbau der Zusammensetzung durch Mikroorganismen zu verhindern, und
(i) Wasser.
2. Zusammensetzung nach Anspruch 1, worin das Petrolatum weißes Petrolatum (Vaseline) ist und das Bienenwachs weißes Wachs ist.
3. Zusammensetzung nach Anspruch 2, worin die Menge des weißen Petrolatum 20 bis 30% beträgt, die Menge des weißen Wachses 7 bis 12% beträgt, die Menge des Sorbits 7 bis 14% beträgt, die Menge des Propylen-glycols 3 bis 8% beträgt und der HLB-Wert der Emulgatoren innerhalb des Bereichs von 4 bis 6 liegt.
4. Zusammensetzung nach irgendeinem der Ansprüche 1 bis 3, weiterhin umfassend
(j) 3 bis 15% Cyclomethicone.
5. Zusammensetzung nach Anspruch 4, umfassend etwa
(a) 0,06% Betamethason-dipropionat,
(b) 25% weißes Petrolatum,
(c) 10% weißes Wachs,
(d) 10,5% Sorbit,
(e) 5% Propylenglycol,
(f) 0,3% einbasiges Natriumphosphat-monohydrat und 0,001% Phosphorsäure,
(g) 0,05% Ceteth 20 und 3% Glycerinoleat,
(h) 0,1% 4-Chloro-m-cresol,
(i) Wasser und
(j) 7% Cylomethicone.
6. Zusammensetzung nach Anspruch 4, umfassend etwa
(a) 0,06% Betamethason-dipropionat,
(b) 30% weißes Petrolatum,
(c) 7% weißes Wachs,
(d) 10,5% Sorbit,
(e) 5% Propylenglycol,
(f) 0,07% Citronensäure-monohydrat und 0,2% Trinatriumcitrat-dihydrat,
(g) 0,05% Ceteth 20 und 3% Glyceryloleat,
(h) 0,1% 4-Chloro-m-cresol,
(i) Wasser und
(j) 5% Cylomethicone.
7. Zusammensetzung nach Anspruch 4, umfassend etwa
(a) 0,06% Betamethason-dipropionat,
(b) 20% weißes Petrolatum,
(c) 10% weißes Wachs,
(d) 10,5% Sorbit,
(e) 5% Propylenglycol,
(f) 0,001% Phosphorsäure und 0,3% einbasiges Natriumphosphat-monohydrat,
(g) 0,05% Ceteth 20 und 3% Glycerinoleat,
(h) 1% Benzylalkohol,
(i) Wasser und
(j) 10% Cylomethicone.
8. Zusammensetzung nach Anspruch 4, umfassend etwa
(a) 0,06% Betamethason-dipropionat,
(b) 30% weißes Petrolatum,
(c) 5% weißes Wachs,
(d) 7% Sorbit,
(e) 5% Propylenglycol,
(f) 0,001% Phosphorsäure und 0,3% einbasiges Natriumphosphat-monohydrat,
(g) 1% Polysorbat 60 und 4% Sorbitansesquioleat,
(h) 0,1% 4-Chloro-m-cresol,
(i) Wasser und
(j) 5% Cylomethicone.
EP84114635A 1983-12-09 1984-12-01 Betamethazondipropionat-Creme Expired EP0146065B1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT84114635T ATE44462T1 (de) 1983-12-09 1984-12-01 Betamethazondipropionat-creme.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US559671 1983-12-09
US06/559,671 US4489071A (en) 1983-12-09 1983-12-09 Betamethasone dipropionate cream

Publications (3)

Publication Number Publication Date
EP0146065A2 EP0146065A2 (de) 1985-06-26
EP0146065A3 EP0146065A3 (en) 1985-08-07
EP0146065B1 true EP0146065B1 (de) 1989-07-12

Family

ID=24234538

Family Applications (1)

Application Number Title Priority Date Filing Date
EP84114635A Expired EP0146065B1 (de) 1983-12-09 1984-12-01 Betamethazondipropionat-Creme

Country Status (15)

Country Link
US (1) US4489071A (de)
EP (1) EP0146065B1 (de)
AT (1) ATE44462T1 (de)
AU (1) AU565947B2 (de)
CA (1) CA1238276A (de)
DE (1) DE3478899D1 (de)
DK (1) DK164022C (de)
GR (1) GR81129B (de)
HK (1) HK42292A (de)
IE (1) IE58042B1 (de)
IL (1) IL73626A (de)
MY (1) MY100049A (de)
NZ (1) NZ210356A (de)
SG (1) SG38892G (de)
ZA (1) ZA849231B (de)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101167730B (zh) * 2007-10-24 2010-11-24 严洁 一种复方倍他米松混悬型注射液

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3534742A1 (de) * 1985-09-28 1987-04-09 Beiersdorf Ag Hydrocortisondiester enthaltende w/o-creme
US4808610A (en) * 1986-10-02 1989-02-28 Schering Corporation Mometasone furoate anti-inflammatory cream composition using hexylene glycol
US4775529A (en) * 1987-05-21 1988-10-04 Schering Corporation Steroid lotion
US5241925A (en) * 1988-12-27 1993-09-07 Dermamed Apparatus and techniques for administering veterinary medicaments
US5332577A (en) * 1988-12-27 1994-07-26 Dermamed Transdermal administration to humans and animals
US5324521A (en) * 1989-12-18 1994-06-28 Dermamed Systems for transdermal administration of medicaments
US5512278A (en) * 1994-01-11 1996-04-30 Phylomed Corporation Ointment base useful for pharmaceutical preparations
US7544674B2 (en) * 2002-10-25 2009-06-09 Galderma S.A. Topical skin care composition
FR3039399B1 (fr) * 2015-07-31 2018-08-24 Idl International Drug Licensing Creme pour l'admnistration de steroides et son procede de preparation

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4070462A (en) * 1976-10-26 1978-01-24 Schering Corporation Steroid ointment
US4346086A (en) * 1981-06-09 1982-08-24 Beiersdorf Aktiengesellschaft Corticosteroid-containing cream
ATE55898T1 (de) * 1983-01-26 1990-09-15 Procter & Gamble Kosmetische stifte.

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CTFA Cosmetic Ingredient Dictionary, pp. 45,46,60 *
Remington's Pharmaceutical, pp. 60, 334 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101167730B (zh) * 2007-10-24 2010-11-24 严洁 一种复方倍他米松混悬型注射液

Also Published As

Publication number Publication date
GR81129B (en) 1985-04-01
US4489071A (en) 1984-12-18
HK42292A (en) 1992-06-19
DE3478899D1 (en) 1989-08-17
AU3598084A (en) 1985-06-13
DK164022C (da) 1992-09-28
AU565947B2 (en) 1987-10-01
EP0146065A3 (en) 1985-08-07
ZA849231B (en) 1985-07-31
EP0146065A2 (de) 1985-06-26
IE58042B1 (en) 1993-06-16
DK582284D0 (da) 1984-12-06
MY100049A (en) 1989-06-29
ATE44462T1 (de) 1989-07-15
NZ210356A (en) 1987-04-30
IL73626A0 (en) 1985-02-28
CA1238276A (en) 1988-06-21
DK582284A (da) 1985-06-10
SG38892G (en) 1992-05-22
DK164022B (da) 1992-05-04
IE843002L (en) 1985-06-09
IL73626A (en) 1987-12-31

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